Search Results (2,051)

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus which affects individuals with both type 1 and type 2 diabetes mellitus (T2DM), presenting with sensory loss, pain, and progressive nerve dysfunction. DPN pathogenesis is multifactorial: chronic hyperglycemia activates the polyol, hexosamine, and protein kinase C (PKC) pathways, increases advanced glycation end-products, and drives oxidative stress, mitochondrial dysfunction, inflammation, and impaired neurotrophic signaling. In addition to hyperglycemia-driven mechanisms, dyslipidemia and microvascular insufficiency exacerbate neural ischemia and metabolic stress. Recent mechanistic, animal, and associative human studies further implicate amyloidogenic toxicity, particularly from human islet amyloid polypeptide (hIAPP), as a plausible contributory factor in peripheral nerve degeneration in T2DM, linking protein misfolding and aggregation to axonal damage and demyelination in DPN. Despite increased understanding of these mechanisms, current treatments remain mainly symptomatic. Emerging therapeutic strategies, including antioxidants, anti-inflammatory agents, modulators of mitochondrial function, amyloid oligomer modulators, neurotrophic enhancers, and regenerative approaches such as stem cells and gene-based therapies, offer potential to modify disease progression. The strength of evidence across these methods varies, ranging from mechanistic and animal studies to early human research and, in some cases, randomized clinical trials. Therefore, although several candidates show potential to alter the disease, few have demonstrated consistent benefits on objective measures of nerve structure or function in large clinical trials. This review summarizes the key mechanisms driving DPN in T2DM and highlights promising therapeutic innovations poised for clinical translation. Full article

Alzheimer’s disease (AD) is the leading cause of dementia, responsible for approximately 60–70% of cases globally. AD is a gradually progressive neurodegenerative disorder that is characterized by widespread deposition of β-amyloid (Aβ) plaques, followed by aggregation of tau protein in the neocortex, neurodegeneration, and cognitive decline. Within these complex pathological interactions, Aβ and tau proteins, together with astrogliosis, neuroinflammation, and other factors, play a key role in the development of clinical AD. Accumulating evidence indicates that the formation of protein oligomers, followed by their aggregation into pathological fibrils, constitutes an early and critical step in the pathogenesis of the disease. Specific pathological proteins are often treated as biomarkers of particular diseases because their presence, concentration, or altered structure reflects an underlying disease process. It is well established that the Aβ and tau proteins are the key hallmarks of AD, and their mutual interaction may significantly influence the pathology of the disease. Early diagnosis is crucial for maximizing the therapeutic benefits of currently available symptomatic treatments, which can alleviate symptoms and modestly delay clinical deterioration in patients with AD. This review highlights the mechanisms involved in protein-dependent neurodegeneration and describes both traditional and novel approaches for the cure of AD. The most important aspect of this publication is the integration of the two key proteins: Aβ and tau, and the resulting shift toward a new therapeutic approach. Full article

Alzheimer’s disease (AD) remains an incurable neurodegenerative disorder. The concept of theranostics—combining diagnostic and therapeutic functions within a single nanoplatform—has been explored for over a decade. Despite a growing number of publications, no theranostic system has yet reached clinical application for AD. This critical review analyzes the fundamental conceptual contradictions that hinder the clinical translation of theranostic nanoplatforms for AD and identifies alternative strategies where nanotechnology may still be beneficial. The review presents key aspects essential for understanding theranostics challenges: AD molecular targets, analysis of existing nanoplatforms, identification of three inherent conceptual conflicts, and viable alternative approaches. Our analysis reveals three core conceptual conflicts: the pharmacokinetic conflict, where diagnostics demand rapid accumulation and clearance while therapy requires prolonged retention—exacerbated by minimal brain delivery (1–2% ID/g) and peripheral toxicity risks; the dose conflict, characterized by orders-of-magnitude disparities between diagnostic and therapeutic dosing, rarely quantified for identical particles; and the temporal conflict, pitting one-time diagnostics against chronic therapy needs, as long-persisting particles generate irremovable brain background signals. We further identify a pervasive methodological trap: predominant focus on mature β-amyloid (Aβ) fibrils overlooks soluble oligomers as the primary toxic species. We conclude by proposing viable alternatives: preclinical intervention for time-limited “hit-and-clear” applications; coordinated theranostic monitoring with separate diagnostics/therapy; theranostic pairs using ligand-matched, function-optimized particles; and external stimuli for temporal function separation. A practical roadmap guides the transition from conceptual demonstrations to clinical translation. Addressing these contradictions can transform theranostics from elegant chemical constructs into clinically meaningful AD tools. Full article

The enzymatic saccharification of cellulose remains a key step in biomass conversion processes, often influenced by enzyme stability, distribution, and accessibility at solid–liquid interfaces. Immobilization of cellulolytic enzymes on nanostructured supports has been proposed as a strategy to modulate catalytic behavior; however, the relationship between enzyme loading and catalytic response remains insufficiently understood. In this study, CuO-based nanobiocatalysts were prepared through controlled cellulase immobilization and systematically evaluated under defined experimental conditions. Structural and physicochemical characterization was performed using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and integrated thermal analysis (TGA–DTG–DSC), enabling a comparative assessment of the analyzed systems. SEM analysis showed that the average particle diameter increased from 39.5 ± 14.8 nm (CuO nanoparticles) to 95.6 ± 21.8 nm (NPI10), 106.6 ± 27.7 nm (NPI15), and 113.5 ± 23.1 nm (NPI20), indicating progressive variations in particle organization with increasing enzyme loading. Catalytic performance was evaluated through enzymatic hydrolysis of cellulose filter paper as a model substrate, with products quantified by HPLC at a representative reaction time. The system prepared at lower enzyme loading (NPI10) exhibited product formation comparable to that of the free enzyme, with apparent average glucose formation values of 1.054 and 1.047 mg·mL⁻¹·h⁻¹, respectively. In contrast, higher immobilization levels were associated with reduced catalytic output. Across all systems, glucose was the predominant product, with negligible accumulation of intermediate oligomers under the evaluated conditions. These results indicate that increasing enzyme loading does not correspond to proportional increases in product formation and highlight the influence of enzyme distribution and accessibility within the system. The combined structural and catalytic observations provide a controlled framework for evaluating how immobilization conditions influence system behavior in nanobiocatalytic systems. Full article

Neurodegenerative diseases arise when normally functional aggregation-prone proteins transition into stable cross-β amyloid fibrils. Although these fibrils share a conserved architecture, the pathways that lead to fibrillation vary across proteins and cellular environments. Liquid–liquid phase separation is now recognized as a central organizer of intracellular biochemistry that modulates protein aggregation. Physiological condensation can buffer aggregation by maintaining macromolecular solubility and providing partner interactions that compete against pathological protein–protein interactions. However, condensates can transform and age into gel-like states that can favor the emergence of β-rich oligomers and solid-state fibrils. Across six disease-linked proteins that include Tau, α-synuclein, amyloid-β, TDP-43, FUS, and hnRNPA1, we compare how sequence-encoded interaction motifs, cellular cofactors, and interfacial microenvironments shape the balance between physiological condensates and pathological amyloids. Here, we highlight the unifying drivers of aggregation and intervention points that preserve native function while limiting toxic amyloid formation. Full article

Oxidative catalytic fractionation (OCF) under the lignin-first strategy has emerged as a critical technological approach for biomass refining. To address the inevitable carbohydrate degradation and lignin condensation in conventional OCF, this study designed a cobalt-doped layered double hydroxide oxide (Co-LDO) catalyst compatible with non-alkaline (without Brønsted bases) organic systems, which exhibits excellent performance in poplar biomass OCF. With a straightforward preparation process, the Co-LDO catalyst yields high-content oxidized lignin oligomers while efficiently retaining carbohydrates, providing feedstock rich in carbohydrates (cellulose and hemicellulose) for the subsequent production of bioenergy and biomass-based chemicals. Under optimized conditions screened via systematic reaction condition investigation and metal-doped LDO catalyst evaluation, the process achieved a 94.01 wt% delignification rate, with 72.19 wt% of lignin converted into lignin oligomer oil, supported by detailed product composition and structural characterization. Meanwhile, 74.14 wt% hemicellulose and 98.23 wt% cellulose were recovered in solid residues, with structurally intact hemicellulose retention being 2.3 times higher than in traditional OCF. Mass balance calculation confirmed a total poplar refining yield of 81.58 wt%. In summary, this Co-LDO-catalyzed OCF strategy provides a high-activity non-precious metal system, effectively suppressing lignin condensation while preserving high-yield carbohydrates, realizing the efficient full-component refining of poplar biomass. Full article

Actinidia arguta is a valuable plant resource known for its diverse bioactive constituents. However, organ-dependent metabolic variation remains insufficiently explored. In this study, an integrated approach combining LC–QTOF–MS-based metabolomic profiling, multivariate analysis, and phytochemical isolation was employed to investigate metabolic differences among fruits, leaves, and roots of A. arguta. Comparative LC–QTOF–MS profiling and principal component analysis (PCA) revealed clear organ-specific metabolic differentiation. The root extract formed a distinct cluster, primarily characterized by flavan-3-ol oligomers, including procyanidin dimers and a trimer. Targeted isolation and spectroscopic analysis identified these compounds as major constituents of the root. Quantitative analysis showed that the root exhibited the highest antioxidant activity (60.8 ± 6.2%) and total phenolic content (10.8 ± 0.7 mg GAE/g dried weight), followed by leaves and fruits, indicating significant organ-dependent variation. The enhanced antioxidant activity observed in the root extract was consistent with the enrichment of oligomeric procyanidins, which are known for their strong radical-scavenging capacity. These findings demonstrate pronounced organ-specific metabolic specialization in A. arguta, with the root characterized by a condensed tannin–dominant chemical profile. This study highlights the potential of root-derived procyanidins as bioactive natural products and provides a basis for their utilization in functional and phytochemical applications, as well as insights into plant defense-related metabolism. Full article

Oligomeric species of alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin are established molecular biomarkers for Parkinson’s disease (PD). However, existing research has yet to fully explore the diagnostic potential of non-phosphorylated α-syn and other cutaneous morphometric parameters, such as variations in collagen type IV within the dermis and epidermis or α-syn expression in melanocytes. This study aims to evaluate and compare the diagnostic utility of these skin morphometric parameters in differentiating 32 PD patients from 19 healthy subjects (HSs), while also examining their correlation with salivary α-syn oligomer levels. Skin biopsies were analyzed via immunofluorescence and confocal microscopy, while salivary oligomeric α-syn was quantified through competitive ELISA. Results revealed a significant reduction in α-syn-positive fibres in PD patients compared to HSs (0.91; <0.0001). Conversely, the collagen staining area and the number of α-syn-positive melanocytes were significantly increased in the skin of PD patients. Specifically, the collagen type IV staining area was significantly higher in the dermis and surrounding the sweat glands of PD patients, demonstrating optimal diagnostic power (0.9448; <0.0001). Similarly, the increase in α-syn-positive melanocytes in PD patients showed robust diagnostic potential (0.84; <0.001). Salivary α-syn oligomers accurately discriminated between PD and HS groups. Furthermore, significant correlations were found between collagen type IV and melanocyte morphometric parameters and various clinical scores in PD. Our findings highlight how multimodal morphometric analysis of the skin can enhance diagnostic accuracy in PD, supporting the use of salivary and cutaneous biomarkers as complementary tools that may reflect distinct aspects of PD pathology. Full article

Design and fabrication of high-performance organic semiconductors are still challenging. Here, we designed new D-(A)n type zinc porphyrin end-capped ethynylene-7-(4-hexyl-thiophen-2-yl)-2,1,3-benzothiadiazole (EBTT) oligomers by linking 5,10,15-trisphenyl porphyrin zinc (ZnTPP) with length-variable EBTT oligomers (at the 20-position of porphyrin) [ZnTPP(EBTT)_n (n = 1–6)]. The influence of oligomer length on molecular structures, orbital energies, electronic absorption spectra, ionization energies, electronic affinities, and reorganization energies was systematically studied through density functional theory. The charge-carrier mobility of the simulated crystals and the power conversion efficiencies (PCE) using PCBM as the accepter were also predicted. ZnTPP(EBTT)₆ show excellent hole/electron mobility of 76.161/9.395 cm²V⁻¹s⁻¹ and extremely high PCE of 25.45%. This work would have significance for the design and synthesis of organic semiconductor materials with large charge-carrier mobility and high PCE performance. Full article

Alzheimer’s (AD) and Parkinson’s disease (PD) are prominent neurodegenerative disorders characterized by early synaptic loss, which correlates more closely with clinical symptoms than neuronal death. This synaptic impairment is primarily driven by disruptions in synaptic vesicle (SV) trafficking, a critical process for maintaining synaptic integrity through a tightly regulated cycle involving clustering, docking-priming, Ca²⁺-triggered fusion, and endocytosis. In AD, amyloid-β (Aβ) oligomers interfere with SNARE-mediated fusion and endocytosis, while hyperphosphorylated tau obstructs vesicle mobility and docking, resulting in cumulative toxicity that aggravates SV defects. Conversely, in PD, α-synuclein (α-syn) aggregation alters vesicle clustering, membrane fusion, and recycling, and these effects are further influenced by Leucine-rich repeat kinase 2 (LRRK2)-Rab-related trafficking defects and the selective vulnerability of dopaminergic terminals. Different from previous reviews that address synaptic dysfunction in a broader manner, the present review is specifically organized around the SV trafficking cycle and compares both shared presynaptic endpoints and disease-specific upstream mechanisms in AD and PD. In addition, recent mechanism-oriented therapeutic strategies are summarized. This vesicle-cycle-centered perspective may provide a clearer framework for understanding presynaptic pathology and for guiding the development of earlier and more targeted interventions. Full article

Chitooligosaccharides (COS) are short-chain chitosan derivatives with a wide range of biomedical, agricultural, and environmental applications, including antimicrobial therapy, wound healing, and pollutant removal. Reliable quantification of COS is essential but currently relies on high-performance liquid chromatography, mass spectrometry, or capillary electrophoresis, which require costly equipment, complex sample preparation, and are unsuitable for routine or on-site applications. This study reports a rapid, solvent-free, colorimetric assay for COS based on the reaction of 5% aqueous ninhydrin with free amino groups in McIlvaine buffer. The assay was optimized using glucosamine as a model analyte, yielding maximal sensitivity at pH 7.0. The chromophore generated (Ruhemann’s purple) remained stable for over 120 min after reaction, allowing measurements to be taken without strict time constraints. Calibration was linear from 0.4 to 2.2 mM (R² = 0.9926), with low limits of detection (0.006 mM) and quantification (0.018 mM). Increasing absorbance with COS polymerization degree (DP1–DP6) demonstrates specificity for free amino groups, while N-acetyl glucosamine showed a negligible response. Furthermore, the assay was successfully adapted for solid-phase detection on ninhydrin-pretreated filter paper and nitrocellulose, with enhanced sensitivity. This simple, efficient, and low-cost method provides an accessible alternative to instrumental techniques, supporting COS monitoring in laboratory workflows and enabling portable applications in biomedicine, agriculture, and environmental diagnostics. Full article

This study investigates the key performance-related fuel properties of emulsifier–diesel solutions and ethanol-in-diesel microemulsions. This work begins with the in situ polymerization of long alkyl chain-substituted glycidyl methacrylate (R-GMA) in diesel and the optional presence of a second methacrylate monomer. The resulting diesel-soluble oligomer functions as a nonionic emulsifier. Controlled amounts of ethanol are subsequently incorporated into the emulsifier–diesel solution to form a stable microemulsion, referred to as E-Diesel. This study examines how the structure of the emulsifier influences key fuel properties, including (i) ethanol–diesel miscibility, (ii) gross calorific value, (iii) Ramsbottom carbon residue (% of fuel), (iv) entrapped polycyclic aromatic hydrocarbons (PAHs), and (v) fuel lubricity. Both the hydrophilic–hydrophobic balance and the structure of the emulsifier side chains are found to significantly affect these properties. Compared with neat diesel, oligomeric emulsifiers enable the substantial dispersion of ethanol in diesel (up to 18 wt.%). The resulting fuel exhibits a gross calorific value exceeding the theoretical sum of diesel and ethanol at the same composition (a synergistic effect) and achieves an enhancement in lubricity up to 49.5% relative to neat diesel at a 5% emulsifier loading. Although the presence of emulsifiers leads to an increase in the carbon residue by up to 54.7% compared to neat diesel during controlled pyrolysis, it simultaneously reduces the PAH content in the exhaust. Overall, this study establishes fundamental correlations among microemulsion stability, combustion synergy, carbon residue formulation, and fuel lubricity, which are governed by the structure of the emulsifier. Full article

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its G_i protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive G_i signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis. Full article

Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral factors that restrict the entry of many enveloped viruses, including HIV-1, by modifying host membrane properties and trapping fusion at the hemifusion stage. Beyond blocking entry in target cells, IFITMs also reduce the infectivity of virions produced from IFITM-expressing cells, a phenomenon termed “negative imprinting”. Conserved motifs, such as the amphipathic helix and oligomerization motifs, have been reported to be essential for IFITM-mediated protection of target cells from viral infection. Yet, the impact of IFITM incorporation on progeny virion infectivity remains poorly defined. Here, we show that IFITM3 mutants defective in target cell protection activity still markedly impair HIV-1 fusion/infection upon incorporating into virions, without affecting viral maturation or Env incorporation. Immunofluorescence studies suggest mislocalization of the IFITM3 mutants as the reason for the lack of antiviral activity in target cells. Testing the antiviral activity of chimeras between antiviral and non-antiviral IFITM orthologs failed to clearly identify a domain responsible for reduction of HIV-1 infectivity, suggesting that multiple domains may be required for negative imprinting. Interestingly, co-incorporation of non-antiviral dog IFITM1 with human IFITM3 did not interfere with IFITM3’s negative imprinting activity, despite forming mixed hetero-oligomers. This finding implies a dominant, oligomerization-independent antiviral phenotype of IFITM3 in virions. Our findings suggest that IFITMs may protect target cells and negatively imprint progeny virions through distinct mechanisms, underscoring the need to further characterize the molecular basis for the reduced fusion competence of IFITM-containing HIV-1 particles. Full article

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease (NMD) caused by loss-of-function mutations in the DMD gene. RNA-based therapies, especially antisense oligonucleotides (ASO)-mediated exon skipping and adenosine deaminase acting on RNA (ADAR)-guided RNA editing, have emerged as complementary approaches that modulate pre-mRNA splicing or correct transcripts without altering genomic DNA. Current phosphorodiamidate morpholino oligomer (PMO) drugs targeting exons 51, 53, and 45 provide mutation-class-specific benefit. At the same time, next-generation delivery strategies (e.g., peptide-conjugated PMOs (PPMOs), antibody–oligonucleotide conjugates (AOC), and endosomal-escape vehicles) aim to improve skeletal, cardiac, and diaphragm exposure. In parallel, RNA editing strategies offer a route to correct select nonsense or missense variants at the base level and may, in principle, restore near-native dystrophin expression. Meaningful translation of these modalities requires predictive large-animal models. A genome-edited microminipig (MMP) bearing DMD exon-23 mutations faithfully recapitulates hallmark features of human DMD. That includes early locomotor deficits, elevated serum creatine kinase (CK) and cardiac troponin T, progressive myocardial fibrosis, and a decline in left-ventricular ejection fraction (LVEF), while maintaining a manageable lifespan of approximately 30 months suitable for long-term studies. In particular, the MMP model provides a practical platform for addressing the persistent challenge of efficient therapeutic delivery to the heart and diaphragm through longitudinal dosing, imaging, and biopsy. In this review, we synthesize clinical progress in exon skipping, outline the promise of RNA editing, and integrate recent insights from Duchenne muscular dystrophy model for microminipigs (DMD-MMPs) as an advanced surrogate for preclinical development and translational evaluation. Full article